A medicament delivery device

ABSTRACT

The present disclosure relates to a medicament delivery device. The medicament delivery device comprises a housing, a dispensing mechanism and an actuator. The housing has first and second portions. The dispensing mechanism comprises a reservoir disposed in the housing. The dispensing mechanism is operable to dispense medicament from the reservoir when the reservoir contains medicament. The first portion of the housing comprises a distal end and the second portion is moveable towards the distal end from an initial position to a primed position. The dispensing mechanism is rendered inoperable when the second portion is in the initial portion. The actuator is actuatable to operate the dispensing mechanism when the second portion is in the primed position.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is the national stage entry of InternationalPatent Application No. PCT/EP2017/073720, filed on Sep. 20, 2017, andclaims priority to Application No. EP 16190880.1, filed on Sep. 27,2016, the disclosures of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to a medicament delivery device.

BACKGROUND

A variety of diseases exist that require regular treatment by injectionof a medicament and such injections can be performed by using injectiondevices. Various injection devices for delivering injections ofmedicament are known in the art. Another type of injection pump that isgaining traction is the bolus injector device. Some bolus injectordevices are intended to be used with relatively large volumes ofmedicament, typically at least 1 ml and maybe a few ml. Injection ofsuch large volumes of medicament can take some minutes or even hours.Such high capacity bolus injector devices can be called large volumedevices (LVDs). Generally such devices are operated by the patientsthemselves, although they may also be operated by medical personnel.

SUMMARY

The present disclosure relates to an improved medicament deliverydevice.

There is provided a medicament delivery device comprises: a housinghaving first and second portions; a dispensing mechanism that comprisesa reservoir disposed in the housing, wherein the dispensing mechanism isoperable to dispense medicament from the reservoir when the reservoircontains medicament; and, an actuator, wherein the first portion of thehousing comprises a distal end and the second portion is moveabletowards the distal end from an initial position, wherein actuation ofthe actuator is impeded such that the dispensing mechanism is renderedinoperable, to a primed position, wherein the actuator is actuatable tooperate the dispensing mechanism.

Advantageously, when the second portion of the housing is in the initialposition the patient is prevented from accidentally operating thedispensing mechanism. The patient is able to easily render the actuatoractuatable to enable operation of the dispensing mechanism by moving thesecond portion of the housing towards the first portion of the housing.

In one embodiment, the dispensing mechanism further comprises adispensing member and a biasing member configured to urge the dispensingmember to move in a first direction relative to the housing to expelmedicament from the reservoir when the reservoir contains medicament.

In one embodiment, the biasing member is configured to resilientlydeform when the second portion of the housing is moved from the initialposition to the primed position such that the biasing member exerts abiasing force on the dispensing member to urge the dispensing member inthe first direction. Thus, the biasing member only needs to be primedimmediately before use, rather than being stored in resiliently deformedstate which may otherwise result in degradation of the biasing memberover time causing a reduction in the biasing force.

In one embodiment, the medicament delivery device comprises a dispensinglock that is moveable between a locked state, wherein the dispensingmember is held in position relative to the housing against the biasingforce of the biasing member, and an unlocked state, wherein thedispensing member is able to move in the first direction.

In one embodiment, the actuator is retracted into the housing when thesecond portion is in the initial position to prevent actuation of theactuator and protrudes out of the housing when the second portion is inthe primed position. Advantageously, such a configuration makes it clearto the patient whether the second portion is in the initial or primedposition and prevents the patient from trying to force operation of theactuator.

The actuator may comprise a push button. The medicament delivery devicemay comprise a needle that is configured to protrude from the distal endof the first portion.

In one embodiment, the first and second portions of the housing compriserespective peripheral walls, and wherein the peripheral wall of one ofthe first and second portions is configured to be received within theperipheral wall of the other one of the first and second portions.

In one embodiment, the housing is configured such that the secondportion is slidable relative to the first portion from the initialposition to the primed position. This sliding motion of the secondportion may be easy for the patient to perform, which is particularlyadvantageous if the patient is elderly or infirm.

In one embodiment, at least one of the first and second portionscomprises a screw thread.

In one embodiment, the medicament delivery device comprises a latchconfigured to resist movement of the second portion relative to thefirst portion from the primed position to the initial position. Thishelps to prevent the actuator from being accidentally rendered operable.

In one embodiment, the first and/or second portion of the housingcomprises a filling port for supplying the reservoir with medicament.

The reservoir may contain medicament.

In one embodiment, the distal end of the first portion of the housingcomprises an adhesive layer. Therefore, the first portion may beattached to an injection site of the patient.

In one embodiment, the second portion comprises a proximal end wall and,preferably, the proximal end wall has a substantially flat surface.

In one embodiment, the first portion of the housing comprises a proximalend that is remote to the distal end.

In one embodiment, the reservoir is located between the first and secondportions of the housing.

In one embodiment, the actuator is at least partially received in thesecond portion of the housing. The actuator may be moveably mounted tothe second portion of the housing. The actuator may be slidably mountedto the second portion of the housing. The actuator may be retracted intothe second portion of the housing when the second portion of the housingis in the initial position.

In one embodiment, the first and second portions of the housing define achamber that receives the dispensing mechanism.

There is also provided a method of preparing a medicament deliverydevice comprising a housing having first and second portions, adispensing mechanism that comprises a reservoir disposed in the housing,and an actuator, the method comprising: positioning a distal end of thefirst portion in proximity to an injection site of a patient; and,moving the second portion towards the distal end of the first portionfrom an initial position, wherein actuation of the actuator is impededsuch that operation of the dispensing mechanism is prevented, to aprimed position, wherein the actuator is moveable relative to thehousing to operate the dispensing mechanism to dispense medicament fromthe reservoir to the injection site.

These and other aspects of the invention will be apparent from andelucidated with reference to the embodiments described hereinafter.

BRIEF DESCRIPTION OF THE FIGURES

Embodiments will now be described, by way of example only, withreference to the accompanying drawings, in which:

FIG. 1 is a schematic cross-sectional side view of a medicament deliverydevice according to a first embodiment, wherein a proximal portion ofthe housing is in an initial position;

FIG. 2 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 1, wherein the proximal portion is in a primedposition and a button projects from the proximal portion;

FIG. 3 is a close-up schematic cross-sectional side view of part of themedicament delivery device of FIG. 1;

FIG. 4 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 1, wherein the button is partially depressedinto the housing and a needle is in a retracted position;

FIG. 5 is a close-up schematic cross-sectional side view of a needleextension lock of the medicament delivery device of FIG. 1, wherein apair of needle locking members are moved to an unlocked state;

FIG. 6 is a close-up schematic cross-sectional side view of a dispensinglock of the medicament delivery device of FIG. 1, wherein a pair ofextension locking members are moved to an unlocked state;

FIG. 7 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 1, wherein the needle is in an extended positionand medicament is dispensed from the needle;

FIG. 8 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 1, wherein the needle is in the retractedposition;

FIG. 9A is a close-up schematic cross-sectional side view of a needleretraction lock of the medicament delivery device of FIG. 1, wherein apair of retraction locking members are in a locked state;

FIG. 9B is a close-up schematic cross-sectional side view of the needleretraction lock of the medicament delivery device of FIG. 1, wherein thepair of retraction locking members are in an unlocked state;

FIG. 10 is a schematic cross-sectional side view of a medicamentdelivery device according to a second embodiment, wherein a proximalportion of the housing is in an initial position;

FIG. 11 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 10, wherein the proximal portion is in a primedposition and a button projects from the proximal portion;

FIG. 12 is a schematic cross-sectional side view of a medicamentdelivery device according to a third embodiment, wherein a proximalportion of the housing is in an initial position;

FIG. 13 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 12, wherein the proximal portion is in a primedposition and a button projects from the proximal portion;

FIG. 14 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 12, wherein the button is depressed into thehousing and a needle is in an extended position;

FIG. 15 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 12, wherein the needle is in the extendedposition and medicament is dispensed from the needle; and,

FIG. 16 is a schematic cross-sectional side view of the medicamentdelivery device of FIG. 12, wherein the needle is in the retractedposition.

DETAILED DESCRIPTION

A medicament delivery device, as described herein, may be configured toinject a medicament into a patient. For example, delivery could besub-cutaneous, intra-muscular, or intravenous. Such a device could beoperated by a patient or care-giver, such as a nurse or physician, andcan include various types of safety syringe, pen-injector, orauto-injector. The device can include a cartridge-based system thatrequires piercing a sealed ampule before use. Volumes of medicamentdelivered with these various devices can range from about 0.5 ml toabout 2 ml. Yet another device can include a large volume device (“LVD”)or patch pump, configured to adhere to a patient's skin for a period oftime (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a “large”volume of medicament (typically about 2 ml to about 10 ml).

In combination with a specific medicament, the presently describeddevices may also be customized in order to operate within requiredspecifications. For example, the device may be customized to inject amedicament within a certain time period (e.g., about 3 to about 20seconds for auto-injectors, and about 10 minutes to about 60 minutes fora large volume device). Other specifications can include a low orminimal level of discomfort, or to certain conditions related to humanfactors, shelf-life, expiry, biocompatibility, environmentalconsiderations, etc. Such variations can arise due to various factors,such as, for example, a drug ranging in viscosity from about 3 cP toabout 50 cP. Consequently, a drug delivery device will often include ahollow needle ranging from about 25 to about 31 Gauge in size. Commonsizes are 27 and 29 Gauge.

FIGS. 1 to 9B show a medicament delivery device 10, which in theexemplary embodiment comprises a bolus injector device, according to afirst embodiment. The medicament delivery device 10 may be in the formof a large volume device.

The medicament delivery device 10 comprises a housing 11, a needle 12, aneedle actuating mechanism 13, a dispensing mechanism 14 and an actuator15.

The housing 11 comprises a distal portion 16 and a proximal portion 17.The term “distal” refers to a location that is relatively closer to asite of injection and the term “proximal” refers to a location that isrelatively further away from the injection site.

The distal portion 16 of the housing 11 comprises a cylindricalperipheral wall 18 and an end wall 19 that together have a generallyU-shaped cross-section. The distal portion 16 of the housing 11 furthercomprises a cylindrical internal wall 16A that is arrangedconcentrically with the cylindrical peripheral wall 18 of the distalportion 16. The proximal portion 17 of the housing 11 comprises acylindrical peripheral wall 20 and an end wall 21 that together have agenerally U-shaped cross-section. The proximal portion 17 of the housing11 comprises a cylindrical internal wall 17A that is arrangedconcentrically with the cylindrical peripheral wall 20 of the proximalportion 17.

The peripheral wall 18 of the distal portion 16 of the housing 11 isslidably received in the peripheral wall 20 of the proximal portion 17such that the end wall 19 of the distal portion 16 is spaced from theend wall 21 of the proximal portion 17 and a recess 22 is formedtherebetween. The distal and proximal portions 16, 17 of the housing 11together form a generally cylindrical shape that has a central axis (seethe dashed line A-A in FIG. 2).

The end wall 19 of the distal portion 16 has an outer surface 19A and aninner surface 19B and the end wall 21 of the proximal portion 17 has anouter surface 21A and an inner surface 21B. One or both of the outersurfaces 19A, 21A of the end walls 19, 21 of the distal and proximalportions 16, 17 may be substantially flat.

The outer surface 19A of the end wall 19 of the distal portion 16comprises an adhesive layer (not shown) that is initially covered by alabel (not shown). In use, the label is removed from the adhesive layerand then the adhesive layer is stuck to the patient's skin at theinjection site of the patient such that the end wall 19 of the distalportion 16 is adhered to the injection site.

The dispensing mechanism 14 comprises a medicament reservoir 23, adispensing member 24, a dispensing biasing member 25 and a dispensinglock 26.

The medicament reservoir 23 is in the form of an annular flexible bag23. The flexible bag 23 is disposed in the recess 22 in the housing 11and abuts the inner surface 19B of the end wall 19 of the distal portion16. The flexible bag 23 is fluidly connected to an aperture 18A in theperipheral wall 18 of the distal portion 16. The aperture 18A forms afilling port 18A that allows for the flexible bag 23 to be filled withmedicament through the peripheral wall 18 of the distal portion 16. Theflexible bag 23 and/or the aperture 18A may comprise a one-way valve(not shown) that is configured to prevent medicament from flowing out ofthe flexible bag 23 via the aperture 18A. Alternatively, oradditionally, a bung (not shown) may be provided that is inserted intothe aperture 18A to seal the aperture 18A after the flexible bag 23 hasbeen filled with medicament.

The dispensing member 24 is in the form of a plate 24. The plate 24 maybe annular. The plate 24 is disposed in the recess 22 in the housing 11such that the flexible bag 23 is located between a distal-facing surface24A of the plate 24 and the inner surface 19B of the end wall 19 of thedistal portion 16. The plate 24 is slidable in the recess 22 in thedirection of the central axis A-A of the housing 11 such that the plate24 is moveable relative to flexible bag 23.

The dispensing biasing member 25 is in the form of a dispensing spring25. The dispensing spring 25 may be a helical spring. The dispensingspring 25 is disposed in the recess 22 in the housing 11 and extendsabout the central axis A-A of the housing 11. The dispensing spring 25is positioned between the internal wall 17A of the proximal portion 17and the peripheral wall 20 of the proximal portion 17.

The dispensing spring 25 is disposed on the opposite side of the plate24 to the flexible bag 23. A first end of the dispensing spring 25 islocated against the inner surface 21B of the end wall 21 of the proximalportion 17 and a remote second end of the dispensing spring 25 islocated against a proximal-facing surface 24B of the plate 24.

The proximal portion 17 is moveable relative to the distal portion 16 ofthe housing 11 between an initial position (shown in FIG. 1) and aprimed position (shown in FIGS. 2, 4, 7 and 8). When the proximalportion 17 is in the initial position, the end wall 21 of the proximalportion 17 is spaced from the plate 24 and the end wall 19 of the distalportion 16 such that the dispensing spring 25 is substantiallyuncompressed. Furthermore, when the proximal portion 17 is in theinitial position, only a small section of the peripheral wall 18 of thedistal portion 16 is received in the peripheral wall 20 of the proximalportion 17.

When the proximal portion 17 is moved to the primed position, the endwall 21 of the proximal portion 17 is moved towards the end wall 19 ofthe distal portion 16 such that the distance between the end walls 19,21 is reduced. An increased amount of the peripheral wall 18 of thedistal portion 16 is received in the peripheral wall 20 of the proximalportion 17 when the proximal portion 17 is in the primed position.

The dispensing lock 26 comprises a pair of dispensing locking members 27that are connected to the distal portion 16 of the housing 11 bycorresponding pivotal couplings 28. Each of the dispensing lockingmembers 27 comprises an elongate member 29 and a projection 30 that isintegrally formed with the elongate member 29.

The elongate members 29 have a first end 29A and a second end 29B. Theelongate members 29 are each attached to a corresponding pivotalcoupling 28 towards the first end 29A of the elongate members 29. Thesecond end 29B of each elongate member 29 is spaced from thecorresponding pivotal coupling 28 such that each second end 29B ispivotable about the corresponding pivotal coupling 28. A recess 29C isprovided in the second end 29B of each elongate member 29.

The projection 30 of each dispensing locking member 27 extends at anangle from a corresponding elongate member 29 and is located proximateto the first end 29A of the elongate member 29. Each projection 30 has afree end 30A that is remote to said corresponding elongate member 29.The elongate member 29 and projection 30 may be arranged such that thedispensing locking members 27 are each generally L-shaped or V-shaped.

The dispensing locking members 27 are pivotable from a locked state(shown in FIGS. 2 and 3) to an unlocked state (shown in FIGS. 4 and 6).In the locked state, each of the dispensing locking members 27 ispositioned such that the elongate member 29 extends towards the end wall21 of the proximal portion 17 at an angle away from the central axis A-Aof the housing 11 in the direction from the first end 29A to the secondend 29B of the elongate member 29. Moreover, in the locked state, thedispensing locking members 27 are positioned such that the projections30 extend towards the end wall 21 of the proximal portion 17 at an angletowards the central axis A-A of the housing 11 in the direction towardsthe free end 30A of the projection 30.

When the dispensing locking members 27 are in the locked state, theplate 24 is located in the recesses 29C of the elongate members 29 suchthat the plate 24 is prevented from moving towards the end wall 19 ofthe distal portion 16 of the housing 11. The configuration of therecesses 29C is such that a portion of each elongate member 29 abuts aradially inwardly facing surface 24C of the plate 24 and therefore, whenthe dispensing locking members 27 are in the locked state and abut theplate 24, the dispensing locking members 27 are prevented from rotatingin a direction wherein the second ends 29B of the elongate members 29move radially outwardly away from the central axis A-A of the housing11.

The dispensing locking members 27 are moveable to the unlocked state,wherein the dispensing locking members 27 are rotated (in the directionof arrow ‘B’ in FIG. 6) such that the second end 29B of each elongatemember 29 and the free end 30A of the corresponding projection 30 pivotabout the respective pivotal couplings 28 to move radially inwardlytowards the central axis A-A of the housing 11. When the dispensinglocking members 27 are in the unlocked state, the second end 29B of eachelongate member 29 is spaced from the plate 24 such that the plate 24 isnot received in the recesses 29C of the elongate members 29. Therefore,the plate 24 is not restricted from moving towards the end wall 19 ofthe distal portion 16 by the dispensing locking members 27.

The actuator 15 is in the form of a button 15 that has a peripheral wall15A and an end wall 15B. The button 15 is received in the proximalportion 17 of the housing 11 such that the peripheral wall 15A of thebutton 15 is located on the inside of the internal wall 17A of theproximal portion 17 and is concentrically aligned therewith. The button15 is slidable within the internal wall 17A of the proximal portion 17in the direction of the central axis A-A of the housing 11.

The needle 12 is moveable relative to the distal portion 16 of thehousing 11 between a retracted position (shown in FIGS. 1 to 4, 8 and9B) and an extended position (shown in FIGS. 7 and 9A). When the needle12 is in the retracted position, the needle 12 is fully received in therecess 22 in the housing 11 such that the needle 12 is shielded toprevent damage to the needle 12 and to protect the patient from beingaccidentally injured by the needle 12.

When the needle 12 is moved from the retracted position to the extendedposition, the needle 12 is moved linearly in the direction of thecentral axis A-A of the housing 11 such that the end of the needle 12projects out of an aperture 19C in the end wall 19 of the distal portion16. Thus, when the adhesive layer of the distal portion 16 is adhered tothe injection site of a patient, the needle 12 pierces the patient'sskin to extend into the injection site to deliver medicament thereto.

The medicament delivery device 10 further comprises a septum 31 that isfixed to the inner surface 19B of the end wall 19 of the distal portion16. The septum 31 is located over the aperture 19C in the end wall 19 ofthe distal portion 16. The needle 12, which is initially in theretracted position, is protected by the septum 31. More specifically,the septum 31 prevents the ingress of contaminants through the aperture19C in the end wall 19 of the distal portion 16 and into contact withthe sterile needle 12. When the needle 12 is moved to the extendedposition, the needle 12 pierces the septum 31 and the end of the needle12 passes through the septum 31 to project from the end wall 19. Theseptum 31 may be manufactured from an impermeable material such asplastic, rubber or metal foil. In alternative embodiments, the septum 31is fixed to the outer surface 19A of the end wall 19 of the distalportion 16 or is located in the aperture 19C in the end wall 19.

The needle actuating mechanism 13 comprises needle extension andretraction biasing members 32, 33, extension and retraction holdingelements 34, 35, and needle extension and retraction locks 36, 37.

The needle extension biasing member 32 is in the form of a needleextension spring 32. The needle extension spring 32 may be a helicalspring. The needle extension spring 32 is located inside the peripheralwall 15A of the button 15 and extends about the central axis A-A of thehousing 11. The needle extension spring 32 is disposed between a base12A of the needle 12 and the extension holding element 34.

The extension holding element 34 is fixed relative to the distal portion16 of the housing 11 and is located on the opposite side of the base 12Aof the needle 12 to the septum 31. The extension holding element 34 isconfigured to act as a stop against which the proximal end of the needleextension spring 32 abuts such that the proximal end of the needleextension spring 32 is prevented from moving towards the end wall 21 ofthe proximal portion 17 in the direction of the central axis A-A of thehousing 11. When the needle 12 is in the initial retracted position, theneedle extension spring 32 is compressed between the base 12A of theneedle 12 and the extension holding element 34 such that the needleextension spring 32 urges the needle 12 away from the extension holdingelement 34 in the direction of the central axis A-A of the housing 11such that the needle 12 is biased to move into the extended position.

The needle extension lock 36 comprises a pair of extension lockingmembers 38 that are connected to the distal portion 16 of the housing 11by respective pivotal couplings 39. Each of the extension lockingmembers 38 comprises an elongate member 38A and first and secondprojections 40, 41 that are integrally formed with the elongate member38A. The first projection 40 is located at the distal end of theelongate member 38A and the second projection 41 is located towards theproximal end of the elongate member 38A.

Each elongate member 38A is attached to the respective pivotal coupling39 at a point between the proximal and distal ends of the elongatemember 38A such that the first and second projections 40, 41 arepivotable about the respective pivotal coupling 39.

The extension locking members 38 are moveable from a locked state (shownin FIG. 3) to an unlocked state (shown in FIG. 5). In the locked state,the extension locking members 38 are positioned such that the elongatemembers 38A extend substantially parallel to the central axis A-A of thehousing 11 and the first projection 40 of each extension locking member38 is located nearer to the end wall 21 of the proximal portion 17 ofthe housing 11 than the second projection 41.

The first projection 40 of each extension locking member 38 extendsradially inwardly towards the central axis A-A of the housing 11 whenthe extension locking members 38 are in the locked state. Each of thefirst projections 40 comprises a proximal-facing surface 40A that abutsthe base 12A of the needle 12 when the extension locking members 38 arein the locked state such that movement of the needle 12 in the directionof the central axis A-A of the housing 11 towards the end wall 19 of thedistal portion 16 is prevented. Thus, when the extension locking members38 are in the locked state, the extension locking members 38 retain theneedle 12 in the retracted position against the force of the needleextension spring 32, which is held in a compressed state between thebase 12A of the needle 12 and the extension holding element 34.

The second projection 41 of each extension locking member 38 extendsradially outwardly away from the central axis A-A of the housing 11 whenthe extension locking members 38 are in the locked state. Each of thesecond projections 41 comprises an angled surface 41A that faces at anangle away from the central axis A-A of the housing 11 and towards theend wall 21 of the proximal portion 17.

The button 15 comprises a lip 15C that extends radially inwardly fromthe inside of the peripheral wall 15A of the button 15 in the directiontowards the central axis A-A of the housing 11. The lip 15C may begenerally annular.

The lip 15C of the button 15 is configured to abut the angled surface41A of both of the extension locking members 38 when the button 15 ismoved within the housing 11 towards the end wall 19 of the distalportion 16. This causes the second projection 41 of each extensionlocking member 38 to be urged radially inwardly towards the central axisA-A such that the extension locking members 38 are rotated from thelocked state to the unlocked state (in the direction of arrow ‘C’ inFIG. 5). In the unlocked state, the first projections 40 are movedradially outwardly such that they no longer abut the base 12A of theneedle 12 and therefore the base 12A of the needle 12 is able to moveaway from the extension holding element 34 under the force of the needleextension spring 32. Thus, when the extension locking members 38 are inthe unlocked state, the needle 12 moves from the retracted position tothe extended position under the force of the needle extension spring 32.

The needle retraction biasing member 33 is in the form of a needleretraction spring 33. The needle retraction spring 33 may be a helicalspring. The needle retraction spring 33 is located inside the distalportion 16 of the housing 11 and extends about the central axis A-Athereof. The needle retraction spring 33 is disposed between theretraction holding element 35 and the septum 31. The septum 31 is fixedrelative to the distal portion 16 of the housing 11 and therefore actsas a stop against which the distal end of the needle retraction spring33 abuts.

The retraction holding element 35 is slidably received in the internalwall 16A of the distal portion 16 of the housing 11. The needleretraction spring 33 is initially compressed between the septum 31 andthe retraction holding element 35 such that the needle retraction spring33 urges the retraction holding element 35 away from the septum 31 inthe direction of the central axis A-A of the housing 11. The needleretraction lock 37 initially retains the retraction holding element 35in position against the force of the needle retraction spring 33 suchthat the needle retraction spring 33 is compressed.

The needle retraction lock 37 comprises a pair of retraction lockingmembers 42 that are connected to the distal portion 16 of the housing 11by respective pivotal couplings 43. Each of the retraction lockingmembers 42 comprises first and second elongate members 44, 45, a recess46, and a projection 47. The first and second elongate members 44, 45are integrally formed at one end. The first and second elongate members44, 45 extend at an angle to each other. In the present embodiment, thefirst and second elongate members 44, 45 of each retraction lockingmember 42 extend substantially perpendicular to each other.

The first and second elongate members 44, 45 comprise respective freeends 44A, 45B that are remote to the pivotal coupling 43. The recess 46is located at the free end 44A of the first elongate member 44 and theprojection 47 is located at the free end 45A of the second elongatemember 45.

The retraction locking members 42 are pivotable from a locked state(shown in FIG. 9A) to an unlocked state (shown in FIG. 9B). In thelocked state, each of the retraction locking members 42 is positionedsuch that the first elongate members 44 extend radially outwardly awayfrom the central axis A-A of the housing 11 and, in one embodiment, aresubstantially perpendicular to the central axis A-A of the housing 11.The free end 44A of each first elongate member 44 overlaps the plate 24in the radial direction. Moreover, in the locked state, each of theretraction locking members 42 is positioned such that the secondelongate members 45 extend towards the end wall 21 of the proximalportion 17 from the respective pivotal coupling 43 and, in oneembodiment, are substantially parallel to the central axis A-A of thehousing 11.

When the retraction locking members 42 are in the locked state, theprojection 47 of each retraction locking member 42 extends radiallyinwardly towards the central axis A-A of the housing 11 to abut aproximal-facing surface of the retraction holding element 35. Thus, theretraction holding element 35 is prevented from moving towards the endwall 21 of the proximal portion 17 and thus the needle retraction spring33 is held in a compressed state between the septum 31 and theretraction holding element 35.

Movement of the plate 24 within the housing 11 towards the end wall 19of the distal portion 16, due to operation of the dispensing mechanism14, causes the plate 24 to be urged against the free end 44A of eachfirst elongate member 44 such that the plate 24 is received in therecess 46 of each first elongate member 44. Thus, the movement of theplate 24 towards the end wall 19 of the distal portion 16 results in aforce being exerted on the free end 44A of each first elongate member44. This force causes the free end 44A of each first elongate member 44to be urged towards the end wall 19 of the distal portion 16 such thateach retraction locking member 42 is urged to rotate about a respectivepivotal coupling 43 from the locked state to the unlocked state (in thedirection of arrow D′ in FIG. 9B).

When the retraction locking members 42 are rotated to the unlockedstate, the projection 47 at the free end 45A of each second elongatemember 45 is moved radially outwardly away from the central axis A-A ofthe housing 11 such that the projections 47 are spaced from theretraction holding element 35. Thus, the projections 47 no longer holdthe retraction holding element 35 in place against the force of theneedle retraction spring 33 and so the retraction holding element 35 ismoved towards the end wall 21 of the proximal end 17 by the needleretraction spring 33.

The needle 12 extends through an aperture 35A in the retraction holdingelement 35 such that when the needle 12 is in the extended position andthe retraction locking members 42 are in the locked state (as shown inFIG. 9A) the base 12A of the needle 12 is located in proximity to theretraction holding element 35. Thus, when the retraction locking members42 are subsequently moved to the unlocked state, the retraction holdingelement 35 is released such that the needle retraction spring 33 urgesthe retraction holding element 35 against the base 12A of the needle 12to move the needle 12 towards the end wall 21 of the proximal portion 17and into the retracted position (as shown in FIG. 9B).

A clearance gap (not shown) may be provided between each retractionlocking member 42 and the septum 31 and end wall 19 of the distalportion 16 to facilitate movement of the retraction locking members 42between the locked and unlocked states. Alternatively, the septum 31 maybe manufactured from a flexible material that facilitates movement ofthe retraction locking members 42.

The medicament delivery device 10 further comprises a coupling 48between the distal and proximal portions 16, 17 of the housing 11. Thecoupling 48 is configured to resist the proximal portion 17 from beingmoving away from the primed position towards the initial position. Thecoupling 48 may be configured to prevent the force of the dispensingspring 25, which is located between the plate 24 and the end wall 21 ofthe proximal portion 17, from moving the end wall 21 of the proximalportion 17 away from the end wall 19 of the distal portion 16 when theproximal portion 17 is in the primed position.

The coupling 48 is in the form of a latch 48. The latch 48 comprisesfirst, second and third stops 49, 50, 51. The first stop 49 is in theform of a first lip 49 that is integrally formed with the peripheralwall 20 of the proximal portion 17 of the housing 11. The first lip 49extends radially inwardly towards the central axis A-A of the housing11. The first lip 49 extends from the end of the peripheral wall 20 ofthe proximal portion 17 that is remote to the end wall 21 of theproximal portion 17. The first lip 49 comprises a proximal-facingsurface 49A.

The second stop 50 is in the form of a second lip 50 that is integrallyformed with the peripheral wall 18 of the distal portion 16. The secondlip 50 extends radially outwardly away from the central axis A-A of thehousing 11. The second lip 50 extends from the end of the peripheralwall 18 of the distal portion 16 that is remote to the end wall 19 ofthe distal portion 16. The second lip 50 comprises a distal-facingsurface 50A.

When the proximal portion 17 of the housing 11 is in the initialposition (as shown in FIG. 1), the proximal-facing surface 49A of thefirst lip 49 abuts the distal-facing surface 50A of the second lip 50 tolimit the range of axial movement between the proximal portion 17 andthe distal portion 16 such that the proximal portion 17 is preventedfrom moving away from the distal portion 16 and being separatedtherefrom.

The third stop 51 is in the form of a recess 51 that extends into theouter surface of the peripheral wall 18 of the distal portion 16. Adistal-facing surface 51A is formed at the edge of the recess 51.

The latch 48 further comprises an angled surface 52 that extends betweenthe distal-facing surface 50A of the second stop 50 and thedistal-facing surface 51A of the third stop 51. The angled surface 52 isangled slightly with respect to the central axis A-A of the housing 11such that the angled surface 52 extends slightly away from the centralaxis A-A of the housing in the direction from the second stop 50 to thethird stop 51. The angled surface 52 is formed from a portion of theouter surface of the peripheral wall 18 of the distal portion 16.

The angled surface 52 is configured such that when the proximal portion17 is moved from the initial position to the primed position the firstlip 49 moves over the angled surface 52 and is urged radially outwardlyby the angled surface 52 such that the first lip 49 is urged away fromthe central axis A-A of the housing 11. The thickness and material ofthe proximal portion 17 is such that when the first lip 49 moves overthe angled surface 52 the peripheral wall 20 of the proximal portion 17resiliently deforms radially outwardly. This flexing of the peripheralwall 20 facilitates movement of the first lip 49 over the angled surface52. Similarly, the distal portion 16 may also have a thickness and/or bemanufactured from a material that allows for the peripheral wall 18 ofthe distal portion 16 to flex radially inwardly as the first lip 49moves over the angled surface 52. The distal and proximal portions 16,17 may be manufactured from, for example, plastic or metal.

Movement of the proximal portion 17 from the initial position to theprimed position causes the first lip 49 to move over the angled surface52 from the second lip 50 towards the recess 51.

When the first lip 49 reaches the recess 51, the first lip 49 movesradially inwardly to ‘snap’ into the recess 51 such that theproximal-facing surface 49A of the first lip 49 abuts the distal-facingsurface 51A at the edge of the recess 51. Thus, the proximal portion 17is held in place in the primed position such that the end wall 21 of theproximal portion 17 is resisted from moving away from the end wall 19 ofthe distal portion 16.

The angled surface 52 is arranged to provide a small amount ofresistance to the first lip 49 moving over the angled surface 52 fromthe second lip 50 towards the recess 51, due to the first lip 49 beingurged radially outwardly when the proximal portion 17 is moved towardsthe primed position. Therefore, the patient must overcome a small amountof resistance to move the proximal portion 17 relative to the distalportion 16 from the initial position to the primed position. Thisreduces the likelihood of the proximal portion 17 being accidentallymoved to the primed position.

An exemplary operation of the medicament delivery device 10 will now bedescribed. The medicament delivery device 10 is typically stored in asterile packaging (not shown). The patient first removes the medicamentdelivery device 10 from the sterile packaging. When the medicamentdelivery device 10 is removed from the sterile packaging the proximalportion 17 of the housing 11 is in the initial position, the needle 12is in the retracted position, and the button 15 is retracted into theproximal portion 17 (as shown in FIG. 1) such that the patient is notable to access the button 15 to actuate the button 15. For example, theinner dimension of the internal wall 17A of the proximal portion 17 maybe sufficiently small that the patient is not able to insert a fingerinto the internal wall 17A to access the button 15. Thus, the patient isnot able to depress the button 15 to operate the dispensing mechanism 14to dispense medicament from the flexible bag 23 and thus the dispensingmechanism 14 is rendered inoperable. Moreover, the patient is not ableto operate the needle actuating mechanism 13 to move the needle 12 tothe extended position.

The patient then supplies medicament to the dispensing mechanism 14 ofthe medicament delivery device 10. More specifically, the patientsupplies medicament to the flexible bag 23 via the filling port 18A inthe peripheral wall 18 of the distal portion 16 of the housing 11. Themedicament may be supplied from, for example, a syringe, container, orpressurised canister. In an alternative embodiment, the medicamentreservoir 23 is pre-filled with medicament, in which case the fillingport 18A may be omitted.

The label (not shown) is then removed from the adhesive layer (notshown) on the outer surface 19A of the end wall 19 of the distal portion16. The adhesive layer is then adhered to the patient's skin at theinjection site such that the end wall 19 of the distal portion 16 issecured to the injection site.

The patient then applies a force to the proximal portion 17 of thehousing 11 to move the proximal portion 17 from the initial position tothe primed position. For example, the patient may use one hand to applya force to the outer surface 21A of the distal wall 21 of the proximalportion 17 to push said distal wall 21 towards the distal wall 19 of thedistal portion 16. As the proximal portion 17 is moved towards theprimed position, the dispensing spring 25 is compressed between theinner surface 21B of the distal wall 21 of the proximal portion 17 andthe proximal facing surface 24B of the plate 24 such that a biasingforce is exerted on the plate 24 that urges the plate 24 towards the endwall 19 of the distal portion 16. However, the dispensing lockingmembers 27 are initially in the locked state to hold the plate 24 inposition against the force of the dispensing spring 25.

When the proximal portion 17 reaches the primed position, the first stop49 engages with the third stop 51 such that the proximal portion 17 isretained in the primed position. The dispensing spring 25, which iscompressed, urges the distal wall 21 of the proximal portion 17 awayfrom the plate 24 when the proximal portion 17 is in the primed positionsuch that the proximal portion 17 is biased away from the primedposition by the force of the dispensing spring 25. However, theengagement between the first and third stops 49, 51 is such to preventthe proximal portion 17 from moving away from the primed position underthe force of the dispensing spring 25. Therefore, once the patient hasmoved the proximal portion 17 to the primed position the patient nolonger needs to apply a force to the end wall 21 of the proximal portion17 to retain the proximal portion 17 in the primed position.

The button 15 is received in the internal wall 17A of the proximalportion 17 of the housing 11 such that when the proximal portion 17 ismoved to the primed position the proximal portion 17 slides relative tothe button 15. This causes the button 15 to project from the proximalportion 17 (as shown in FIG. 2). Therefore, the button 15 may beactuated by the patient. The button 15 projects from the end wall 21 ofthe proximal portion 17 when the proximal portion 17 is in the primedposition.

With the proximal portion 17 in the primed position, the medicamentdelivery device 10 is primed for supplying medicament to the injectionsite of the patient. The patient depresses the end wall 15B of thebutton 15 such that the button 15 is slid into the proximal portion 17of the housing 11. This causes the button 15 to engage with the needleextension lock 36 such that the needle extension spring 32 is releasedto move the needle 12 to the extended position. In more detail, thebutton 15 is slid towards the end wall 19 of the distal portion 16 untilthe projection 15C of the button 15 is urged against the angled surface41A of the second projection 41 of each extension locking member 38,resulting in each extension locking member 38 rotating from the lockedstate (shown in FIG. 3) to the unlocked state (shown in FIG. 5). Asdiscussed above, this allows the base 12A of the needle 12 to move awayfrom the extension holding element 34 under the force of the needleextension spring 32 such that the needle 12 moves axially to passthrough the septum 31 to extend out of the aperture 19C in the end wall19 of the distal portion 16. Thus, the needle 12 is moved to theextended position (as shown in FIG. 7). The end wall 19 of the distalportion 16 is adhered to the patient's skin and therefore when theneedle 12 is moved to the extended position the needle 12 enters theinjection site of the patient.

When the needle 12 is moved to the extended position the needle 12 isfluidly communicated with the inside of the flexible bag 23. In oneembodiment, a conduit (not shown) is provided that is fluidly connectedto the inside of the flexible bag 23. The needle 12 comprises anaperture (not shown) that aligns with the conduit to fluidly communicatetherewith when the needle 12 is moved to the extended position such thatmedicament is able to flow out of the flexible bag 23, through theconduit, and into the aperture of the needle 12 to be dispensed from theneedle 12.

The patient continues to push the button 15 into the housing 11 to thenengage the button 15 with the dispensing lock 26 such that, after theneedle 12 has been moved to the extended position, the dispensing spring25 is released to urge the plate 24 towards the end wall 19 of thedistal portion 16 such that medicament is dispensed from the flexiblebag 23. More specifically, the distal end of the button 15 is urgedagainst the free end 30A of the projection 30 of each dispensing lockingmember 27, resulting in each dispensing locking member 27 rotating fromthe locked state (shown in FIG. 3) to the unlocked state (shown in FIG.6). As discussed above, this allows the plate 24 to move towards the endwall 19 of the distal portion 16 under the force of the dispensingspring 25. Therefore, the flexible bag 23 is compressed between theplate 24 and the end wall 19 of the distal portion 16 such that thepressure of the medicament in the flexible bag 23 is increased andtherefore the medicament flows out of the flexible bag 23 and flowsthrough the needle 12 to enter the injection site of the patient.

Once the button 15 has been depressed to the extent that the dispensinglocking members 27 are moved to the unlocked state to commencemedicament delivery, the patient may stop pressing the button 15. Theplate 24 will continue to move towards the end wall 19 of the distalportion 16 such that the flexible bag 23 is compressed and thusmedicament is delivered to the injection site of the patient via theneedle 12. Therefore, the medicament delivery device 10 may be used todeliver medicament to the injection site of the patient over an extendedtime period, for example, several hours, without requiring the patientto continuously apply a force to the button 15.

Medicament will continue to be delivered to the injection site until theplate 24 moves to a position within the housing 11 wherein the plate 24engages with the needle retraction lock 37 such that the needleretraction spring 33 is released to move the needle 12 to the retractedposition. In more detail, the plate 24 is moved towards the end wall 19of the distal portion 16 under the force of the dispensing spring 25until the plate 24 is urged against the free end 44A of each firstelongate member 44 of the retraction locking members 42, resulting ineach retraction locking member 42 rotating from the locked state (shownin FIG. 9A) to the unlocked state (shown in FIG. 9B). As discussedabove, this allows the retraction holding element 35 to move away fromthe end wall 19 of the distal portion 16 under the force of the needleretraction spring 33 such that the retraction holding element 35 isurged against the base 12A of the needle 12 to move the needle 12 intothe housing 11 to the retracted position (as shown in FIGS. 8 and 9B).The patient may then remove the medicament delivery device 10 from theinjection site.

In one embodiment (not shown), a lock may be provided to lock the button15 in position when the proximal portion 17 is in the initial position.The lock may comprise a locking member that is in a locked state whenthe proximal portion 17 is in the initial position to prevent movementof the button 15 relative to the housing 11. The locking member is movedto an unlocked state when the proximal portion 17 is moved to the primedposition such that the button 15 can be moved relative to the housing11.

Referring now to FIGS. 10 and 11, a medicament delivery device 60according to a second embodiment is shown. The medicament deliverydevice 60 of the second embodiment is similar to the medicament deliverydevice 10 of the first embodiment, with like features retaining the samereference numerals. A difference is that the coupling 48 of themedicament delivery device 10 of the first embodiment is omitted and isreplaced with an alternative coupling 61.

The coupling 61 of the medicament delivery device 60 of the secondembodiment comprises first and second screw threads 62, 63. The firstscrew thread 62 is formed in the inner surface of the peripheral wall 20of the proximal portion 17. The second screw thread 63 is formed in theouter surface of the peripheral wall 18 of the distal portion 16.

The first and second screw threads 62, 63 are configured to engage tocouple the distal and proximal portions 16, 17 of the housing 11 suchthat the proximal portion 17 can be screwed to the distal portion 16 ofthe housing 11. Therefore, the proximal portion 17 is moveable from aninitial position (shown in FIG. 10), wherein the proximal portion 17 iscoupled to the distal portion 16 such that the end walls 19, 21 of thedistal and proximal portions 16, 17 are spaced apart, to a primedposition (shown in FIG. 11), wherein the proximal portion 17 is twistedsuch that the screw threads 62, 63 engage and thus the end walls 19, 21of the distal and proximal portions 16, 17 are moved closer together.

The medicament delivery device 60 of the second embodiment comprises aneedle actuating mechanism 13 and a dispensing mechanism 14 that aresimilar to those of the medicament delivery device 10 of the firstembodiment described above.

An exemplary operation of the medicament delivery device 60 will now bedescribed. The medicament delivery device 60 is typically stored in asterile packaging (not shown). The patient first removes the medicamentdelivery device 60 from the sterile packaging. When the medicamentdelivery device 60 is removed from the sterile packaging the proximalportion 17 of the housing 11 is in the initial position, the needle 12is in the retracted position, and the button 15 is retracted into theproximal portion 17 (as shown in FIG. 10) such that the patient is notable to access the button 15 to actuate the button 15. Thus, the patientis not able to depress the button 15 to operate the dispensing mechanism14 to dispense medicament from the flexible bag 23 or operate the needleactuating mechanism 13 to move the needle 12 to the extended position.

The patient then supplies medicament to the flexible bag 23 of themedicament delivery device 60, removes the label (not shown) from theadhesive layer (not shown), and adheres the adhesive layer to thepatient's skin such that the end wall 19 of the distal portion 16 issecured to the injection site.

When the patient wishes to commence the injection, the patient rotatesthe proximal portion 17 relative to the distal portion 16 such that theengagement of the first and second screw threads 62, 63 causes theproximal portion 17 to move from the initial position to the primedposition. More specifically, the rotation of the proximal portion 17relative to the distal portion 16 causes the proximal portion 17 to moverelative to the distal portion 16 in the direction of the central axisA-A of the housing 11 such that the end wall 21 of the proximal portion17 moves towards the end wall 19 of the distal portion 16. The patientmay use one hand to twist the proximal portion 17 relative to the distalportion 16 to move the proximal portion 17 to the primed position.

As the proximal portion 17 is moved towards the primed position, thedispensing spring 25 is compressed between the distal wall 21 of theproximal portion 17 and the plate 24 such that the dispensing spring 25exerts a biasing force on the plate 24 that urges the plate 24 towardsthe end wall 19 of the distal portion 16. However, the dispensinglocking members (not shown) of the dispensing mechanism 14 are initiallyin the locked state to hold the plate 24 in position against the forceof the dispensing spring 25.

When the proximal portion 17 reaches the primed position, the proximalportion 17 is retained in the primed position by the engagement of thefirst and second screw threads 62, 63. The dispensing spring 25, whichis compressed, urges the distal wall 21 of the proximal portion 17 awayfrom the plate 24 when the proximal portion 17 is in the primed positionsuch that the proximal portion 17 is biased away from the primedposition by the force of the dispensing spring 25. However, theconfiguration of the first and second screw threads 62, 63 is such toprevent the proximal portion 17 from moving away from the primedposition under the force of the dispensing spring 25. This may beachieved, for example, due to the pitch of the first and second screwthreads 62, 63. Therefore, once the patient has moved the proximalportion 17 to the primed position the patient no longer needs to apply aforce to the proximal portion 17 to retain the proximal portion 17 inthe primed position.

The actuator 15 protrudes from the end wall 21 of the proximal portion17 when the proximal portion 17 is in the primed position.

The remaining operation of the medicament delivery device 60 is the sameas that of the medicament delivery device 10 of the first embodiment andtherefore, for the sake of brevity, a detailed description thereof isnot repeated hereinafter. Briefly, when the proximal portion 17 is inthe primed position, the patient pushes the button 15 into the proximalportion 17 such that the button 15 engages with the needle extensionlock of the needle actuating mechanism 13 such that the needle extensionspring is released to move the needle 12 to the extended position. Thepatient further presses the button 15 into the proximal portion 17 untilthe button 15 engages with the dispensing lock of the dispensingmechanism 14 such that, after the needle 12 has been moved to theextended position, the dispensing spring 25 is released to urge theplate 24 towards the end wall 19 of the distal portion 16. Therefore,medicament is dispensed from the flexible bag 23. The patient may thenstop pressing the button 15. The plate 24 will continue to move towardsthe end wall 19 of the distal portion 16 such that the flexible bag 23is compressed to dispense medicament to the injection site of thepatient via the needle 12.

Medicament will continue to be delivered to the injection site until theplate 24 moves to a position within the housing 11 wherein the plate 24engages with the needle retraction lock of the needle actuatingmechanism 13 such that the needle retraction spring is released to movethe needle 12 to the retracted position. In this position, the plate 24is urged against the retraction locking members of the needle retractionlock such that further movement of the plate 24 towards the end wall 19of the distal portion 16 is prevented. The patient may then remove themedicament delivery device 60 from the injection site.

In an alternative embodiment, one of the first and second screw threads62, 63 is omitted and is replaced by a protrusion that engages with theother one of the first and second screw threads 62, 63.

Referring now to FIGS. 12 to 16, an injection device 70 according to athird embodiment is shown. The medicament delivery device 70 comprises ahousing 71, a needle 72, a needle actuating mechanism 73, a dispensingmechanism 74, and an actuator 75 in the form of a button 75.

The housing 71 comprises a distal portion 76 and a proximal portion 77.The distal portion 76 comprises a peripheral wall 78 and an end wall 79and the proximal portion 77 comprises a peripheral wall 80 and an endwall 81. The peripheral wall 78 of the distal portion 76 of the housing71 is slidably received in the peripheral wall 80 of the proximalportion 77 such that the end wall 79 of the distal portion 76 is spacedfrom the end wall 81 of the proximal portion 77 and a recess 82 isformed therebetween. The end wall 79 of the distal portion 76 comprisesan adhesive layer (not shown) that is initially covered by a label (notshown). In use, the label is removed from the adhesive layer and thenthe adhesive layer is stuck to the injection site of the patient suchthat the end wall 79 of the distal portion 76 is adhered to theinjection site.

The dispensing mechanism 74 comprises a medicament reservoir 83, adispensing member 84, a dispensing biasing member 85 and a dispensinglock (not shown).

The medicament reservoir 83 is in the form of rigid container 83. Therigid container 83 may be a cylinder 83. The dispensing member 84 is inthe form of a plunger 84 that is slidably received in the cylinder 83.

The dispensing biasing member 85 is in the form of a dispensing spring85. The dispensing spring 85 extends between the plunger 84 and the endwall 81 of the proximal portion 77. The dispensing spring 85 isconfigured to urge the plunger 84 to slide in the cylinder 83 towardsthe end wall 79 of the distal portion 76 to dispense medicament from thecylinder 83.

The proximal portion 77 is moveable relative to the distal portion 76 ofthe housing 71 between an initial position (shown in FIG. 12) and aprimed position (shown in FIGS. 13 to 16). When the proximal portion 77is in the initial position, the end wall 81 of the proximal portion 77is spaced from the plunger 84 such that the dispensing spring 85 issubstantially uncompressed. When the proximal portion 77 is moved to theprimed position, the end wall 81 of the proximal portion 77 is movedtowards the end wall 79 of the distal portion 76 such that the distancebetween said end walls 79, 81 is reduced. The distance between theplunger 84 and the end wall 81 of the proximal portion 77 is alsoreduced such that the dispensing spring 85 is compressed therebetween.

The dispensing mechanism 74 comprises a dispensing lock (not shown) thatis configured to retain the plunger 84 in position relative to thecylinder 83 against the force of the dispensing spring 85. Thedispensing lock of the medicament delivery device 70 of the thirdembodiment is similar to the dispensing lock 26 of the medicamentdelivery device 10 of the first embodiment and therefore, for the sakeof brevity, a detailed description of the dispensing lock will not berepeated hereinafter. The dispensing lock comprises a locking member(not shown) that is moveable from a locked state, wherein the plunger 84in held in position relative to the cylinder 83 against the force of thedispensing spring 85, to an unlocked state, wherein the plunger 84 isable to move in the cylinder 83.

The needle 72 is slidable relative to the distal portion 76 of thehousing 71 between a retracted position (shown in FIGS. 12, 13 and 16),wherein the needle 72 is fully received within the housing 71, and anextended position (shown in FIGS. 14 and 15), wherein the needle 72projects from the end wall 79 of the distal portion 76 of the housing71.

The needle actuating mechanism 73 of the medicament delivery device 70of the third embodiment is similar to the needle actuating mechanism 13of the medicament delivery device 10 of the first embodiment and so adetailed description will not be repeated hereinafter. Briefly, theneedle actuating mechanism 73 includes needle extension and retractionsprings, extension and retraction holding elements, and needle extensionand retraction locks that are configured in a similar manner to those ofthe first embodiment. For example, the needle extension and retractionlocks may comprise corresponding locking members that are moveable froma locked state, wherein the respective extension and retraction springsare held in a compressed position, to an unlocked state, wherein therespective extension and retraction springs are released.

An exemplary operation of the medicament delivery device 70 will now bedescribed. The medicament delivery device 70 is typically stored in asterile packaging (not shown). The patient first removes the medicamentdelivery device 70 from the sterile packaging. When the medicamentdelivery device 70 is removed from the sterile packaging the proximalportion 77 of the housing 71 is in the initial position, the needle 72is in the retracted position, and the button 75 is retracted into theproximal portion 77 (as shown in FIG. 12) such that the patient is notable to access the button 75 to actuate the button 75. Thus, the patientis not able to depress the button 75 to operate the dispensing mechanism74 to dispense medicament from the medicament reservoir 83 or to operatethe needle actuating mechanism 73 to move the needle 72 to the extendedposition. The medicament reservoir 84 may be pre-filled with medicamentor may be filled by the patient via a filling port (not shown).

The patient removes the label (not shown) from the adhesive layer (notshown), and adheres the adhesive layer to the patient's skin such thatthe end wall 79 of the distal portion 76 is secured to the injectionsite.

When the patient wishes to commence the injection, the patient urges theend wall 81 the proximal portion 77 towards to the end wall 19 of thedistal portion 76 such that the proximal portion 77 moves from theinitial position to the primed position. As the proximal portion 77 ismoved towards the primed position, the dispensing spring 85 iscompressed between the plunger 84 and the distal wall 81 of the proximalportion 77 such that a biasing force is exerted on the plunger 84 thatbiases the plunger 84 to move within the cylinder 83 towards the endwall 79 of the distal portion 76. However, the plunger 84 is initiallyheld in position relative to the cylinder 83 by the needle extensionlock (not shown).

When the proximal portion 77 reaches the primed position, the proximalportion 77 is retained in the primed position by a coupling, forexample, a latch (not shown). In another embodiment (not shown), thecoupling comprises a pair of engaging screw threads. The button 75protrudes from the end wall 81 of the proximal portion 77 when theproximal portion 77 is in the primed position.

When the proximal portion 77 is in the primed position, the patientpushes the button 75 into the proximal portion 77 to engage the button75 with the needle extension lock (not shown) such that the needleextension spring is released to move the needle 72 to the extendedposition (as shown in FIG. 14). When the needle 72 moves to the extendedposition, a passage 72B in the base 72A of the needle 72 aligns with aconduit 86 extending from an outlet 83A in the cylinder 83. Thus, thepassage 72B is fluidly communicated with the conduit 86. The patientcontinues to depress the button 75 until the button 75 engages with thedispensing lock (not shown) such that, after the needle 72 has beenmoved to the extended position, the dispensing spring 85 is released tourge the plunger 84 towards the end wall 79 of the distal portion 76.This causes the plunger 84 to move within the cylinder 83 to dispensemedicament from the cylinder 83 (as shown in FIG. 15). The medicamentflows from the outlet 83A in the cylinder 83 and into the conduit 86.The medicament flows through the conduit 86 and enters the passage 72Bin the needle 72 wherein the medicament flows through the needle 72 tothe injection site of the patient. The patient may then stop pressingthe button 75. The plunger 84 will continue to move within the cylinder83 under the force of the dispensing spring 85 to dispense medicamentfrom the cylinder 83. Medicament will continue to be delivered to theinjection site until the plunger 84 moves to a position within thecylinder 83 wherein the plunger 84 engages with the needle retractionlock (not shown) such that the needle retraction spring is released tomove the needle 72 to the retracted position (as shown in FIG. 16). Thepatient may then remove the medicament delivery device 70 from theinjection site.

In the above described embodiments the needle extension and retractionsprings 32, 33 are pre-compressed such that the springs 32, 33 are in acompressed state prior to the proximal portion 17, 77 of the housing 11,71 being moved to the primed position. However, in an alternativeembodiment (not shown), the needle extension and retraction springs 32,33 are in a substantially uncompressed state when the proximal portion17, 77 is in the initial position and movement of the proximal portion17, 77 to the primed position compresses the extension and retractionsprings 32, 33. For example, the extension holding element 34 mayinstead be fixed relative to the proximal portion 17, 77 such thatmovement of the proximal portion 17, 77 from the initial position to theprimed position moves the extension holding element 34 towards the endwall 19, 79 of the distal portion 16, 76. Thus, the needle extensionspring 32 is compressed between the extension holding element 34 and thebase 12A, 72A of the needle 12, 72.

Although in the above described embodiment the proximal portion 17, 77is moved from the initial position to the primed position to compressthe dispensing spring 25, 85, in an alternative embodiment (not shown)the dispensing spring 25, 85 is pre-compressed.

In the above described embodiment the actuator 15, 75 is fully receivedwithin the housing 11, 71 when the proximal portion 17, 77 is in theinitial position. However, in an alternative embodiment, the actuator15, 75 is configured to project from the proximal portion 17, 77 of thehousing 11, 71 when the proximal portion 17, 77 is in the initial andprimed positions. In one such embodiment, the actuator 15, 75 is ofsufficient length to project from the end wall 21, 81 of the proximalportion 17, 77 when the proximal portion 17, 77 is in the initialposition.

In the above described embodiment, the dispensing biasing member 25, 85and the needle extension and retraction biasing members 32, 33 compriserespective springs 25, 85 32, 33. However, in alternative embodiments(not shown) one or more of the dispensing biasing member 25, 85, theneedle extension biasing member 32 and the needle retraction biasingmember 33 comprise a different type of biasing member, for example, aportion of resiliently deformable material that is compressed to exert abiasing force.

In the above described embodiment, the needle 12, 72 is moveablerelative to the housing 11, 71 between the retracted and extendedpositions. However, in an alternative embodiment the needle 12, 72 isfixed in the extended position such that the needle 12, 72 permanentlyprojects from the housing 11, 71. Thus, when the end wall 19, 79 of thedistal portion 16, 76 is secured to the patient's skin the needle 12, 72pierces the skin to enter the injection site of the patient.

In the above described embodiment, the dispensing lock 26 ismechanically operated, the end of the button 15, 75 being urged againstthe dispensing locking members 27 to rotate the dispensing lockingmembers 27 from the locked state to the unlocked state. However, in analternative embodiment the dispensing lock 26 is electrically operated.For example, the dispensing lock may comprise an electromagnetic latch(not shown) that holds the dispensing member 24, 84 in position relativeto the distal portion 16, 76 of the housing 11, 71. When the button 15,75 is depressed by the patient the electromagnetic latch changes statesuch that the dispensing member 24, 84 is released to move towards theend wall 19, 79 of the distal portion 16, 76 under the force of thedispensing spring 25, 85. Similarly, the needle actuating mechanism 13,73 may instead be electrically operated, for example, comprising a motor(not shown) that moves the needle 12, 72 between the retracted andextended positions.

In the above described embodiments, the dispensing mechanism 14, 74comprises a dispensing member 24, 84 and a dispensing biasing member 25,85 configured to urge the dispensing member 24, 84 to move relative tothe housing 11 to expel medicament from the reservoir 23, 83. However,it should be recognised that in alternative embodiments the dispensingmechanism may have a different arrangement. In one embodiment (notshown), the dispensing mechanism comprises a pump that is operable topump medicament from the reservoir to deliver the medicament to theneedle. For example, when the actuator is in the primed position, thepatient may actuate the actuator to operate the pump to delivermedicament from the reservoir. In another embodiment (not shown), thereservoir comprises a barrel for containing medicament, whereinoperation of the dispensing mechanism moves a plunger within the barrelto dispense medicament from the barrel, wherein the plunger is movedrelative to the barrel by a drive mechanism, for example, an electricmotor or a hydraulic or pneumatic drive mechanism. The motor may be alinear motor or may be a rotary motor that drives a rack and pinion gearassembly to move the plunger relative to the barrel.

In some embodiments, actuation of the actuator may close a switch tooperate the dispensing mechanism, for example, to operate a motor of apump to dispense medicament from the reservoir or to operate a drivemechanism to move a plunger. Alternatively actuation of the actuator maybe detected by a sensor, for example, a proximity sensor, wherein thedispensing mechanism is operated upon detection of actuation of theactuator.

The terms “drug” or “medicament” are used herein to describe one or morepharmaceutically active compounds. As described below, a drug ormedicament can include at least one small or large molecule, orcombinations thereof, in various types of formulations, for thetreatment of one or more diseases. Exemplary pharmaceutically activecompounds may include small molecules; polypeptides, peptides andproteins (e.g., hormones, growth factors, antibodies, antibodyfragments, and enzymes); carbohydrates and polysaccharides; and nucleicacids, double or single stranded DNA (including naked and cDNA), RNA,antisense nucleic acids such as antisense DNA and RNA, small interferingRNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids maybe incorporated into molecular delivery systems such as vectors,plasmids, or liposomes. Mixtures of one or more of these drugs are alsocontemplated.

The term “drug delivery device” shall encompass any type of device orsystem configured to dispense a drug into a human or animal body.Without limitation, a drug delivery device may be an injection device(e.g., syringe, pen injector, auto injector, large-volume device, pump,perfusion system, or other device configured for intraocular,subcutaneous, intramuscular, or intravascular delivery), skin patch(e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal orpulmonary), implantable (e.g., coated stent, capsule), or feedingsystems for the gastro-intestinal tract. The presently described drugsmay be particularly useful with injection devices that include a needle,e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other vesselconfigured to provide a suitable chamber for storage (e.g., short- orlong-term storage) of one or more pharmaceutically active compounds. Forexample, in some instances, the chamber may be designed to store a drugfor at least one day (e.g., 1 to at least 30 days).

In some instances, the chamber may be designed to store a drug for about1 month to about 2 years. Storage may occur at room temperature (e.g.,about 20° C.), or refrigerated temperatures (e.g., from about −4° C. toabout 4° C.). In some instances, the drug container may be or mayinclude a dual-chamber cartridge configured to store two or morecomponents of a drug formulation (e.g., a drug and a diluent, or twodifferent types of drugs) separately, one in each chamber. In suchinstances, the two chambers of the dual-chamber cartridge may beconfigured to allow mixing between the two or more components of thedrug or medicament prior to and/or during dispensing into the human oranimal body. For example, the two chambers may be configured such thatthey are in fluid communication with each other (e.g., by way of aconduit between the two chambers) and allow mixing of the two componentswhen desired by a user prior to dispensing. Alternatively or inaddition, the two chambers may be configured to allow mixing as thecomponents are being dispensed into the human or animal body.

The drug delivery devices and drugs described herein can be used for thetreatment and/or prophylaxis of many different types of disorders.Exemplary disorders include, e.g., diabetes mellitus or complicationsassociated with diabetes mellitus such as diabetic retinopathy,thromboembolism disorders such as deep vein or pulmonarythromboembolism. Further exemplary disorders are acute coronary syndrome(ACS), angina, myocardial infarction, cancer, macular degeneration,inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetesmellitus or complications associated with diabetes mellitus include aninsulin, e.g., human insulin, or a human insulin analogue or derivative,a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptoragonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4(DPP4) inhibitor, or a pharmaceutically acceptable salt or solvatethereof, or any mixture thereof. As used herein, the term “derivative”refers to any substance which is sufficiently structurally similar tothe original substance so as to have substantially similar functionalityor activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin, whereinproline in position B28 is replaced by Asp, Lys, Leu, Val or Ala andwherein in position B29 Lys may be replaced by Pro; Ala(B26) humaninsulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30)human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30)human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoylhuman insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin; B29-N—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyhepta¬decanoyl) human insulin. Exemplary GLP-1, GLP-1analogues and GLP-1 receptor agonists are, for example:Lixisenatide/AVE0010/ZP10/Lyxumia,Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acidpeptide which is produced by the salivary glands of the Gila monster),Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide,Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054,Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926,NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697,DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030,CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN andGlucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, acholesterol-reducing antisense therapeutic for the treatment of familialhypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Exemplary hormones include hypophysis hormones or hypothalamus hormonesor regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Exemplary polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)2 fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region.

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful include, forexample, Fab fragments, F(ab′)2 fragments, scFv (single-chain Fv)fragments, linear antibodies, monospecific or multispecific antibodyfragments such as bispecific, trispecific, and multispecific antibodies(e.g., diabodies, triabodies, tetrabodies), minibodies, chelatingrecombinant antibodies, tribodies or bibodies, intrabodies, nanobodies,small modular immunopharmaceuticals (SMIP), binding-domainimmunoglobulin fusion proteins, camelized antibodies, and VHH containingantibodies. Additional examples of antigen-binding antibody fragmentsare known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceuticalformulations comprising (a) the compound(s) or pharmaceuticallyacceptable salts thereof, and (b) a pharmaceutically acceptable carrier.The compounds may also be used in pharmaceutical formulations thatinclude one or more other active pharmaceutical ingredients or inpharmaceutical formulations in which the present compound or apharmaceutically acceptable salt thereof is the only active ingredient.Accordingly, the pharmaceutical formulations of the present disclosureencompass any formulation made by admixing a compound described hereinand a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are alsocontemplated for use in drug delivery devices. Pharmaceuticallyacceptable salts are for example acid addition salts and basic salts.Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from an alkali or alkaline earth metal,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1 C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are known to those of skill in thearts.

Pharmaceutically acceptable solvates are for example hydrates oralkanolates such as methanolates or ethanolates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the substances, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentinvention, which encompass such modifications and any and allequivalents thereof.

1.-18. (canceled)
 19. A medicament delivery device comprising: a housingcomprising a first portion and a second portion; a dispensing mechanismthat comprises a reservoir disposed in the housing, wherein thedispensing mechanism is operable to dispense medicament from thereservoir when the reservoir contains medicament; and an actuator,wherein the first portion of the housing comprises a distal end and thesecond portion of the housing is moveable towards the distal end from aninitial position to a primed position, wherein actuation of the actuatoris impeded such that the dispensing mechanism is rendered inoperablewhen the second portion is in the initial position, and the actuator isactuatable to operate the dispensing mechanism when the second portionis in the primed position.
 20. The medicament delivery device accordingto claim 19, wherein the dispensing mechanism further comprises adispensing member and a biasing member configured to urge the dispensingmember to move in a first direction relative to the housing to expelmedicament from the reservoir when the reservoir contains medicament.21. The medicament delivery device according to claim 20, wherein thebiasing member is configured to resiliently deform when the secondportion of the housing is moved from the initial position to the primedposition such that the biasing member exerts a biasing force on thedispensing member to urge the dispensing member in the first direction.22. The medicament delivery device according to claim 21, furthercomprising a dispensing lock that is moveable between a locked state andan unlocked state, wherein the dispensing member is held in positionrelative to the housing against the biasing force of the biasing memberwhen the dispensing lock is in the locked state, wherein the dispensingmember is able to move in the first direction when the dispensing lockis in the unlocked state.
 23. The medicament delivery device accordingto claim 19, wherein the actuator is retracted into the housing when thesecond portion is in the initial position to prevent actuation of theactuator, and the actuator protrudes out of the housing when the secondportion is in the primed position.
 24. The medicament delivery deviceaccording to claim 19, wherein the actuator comprises a push button. 25.The medicament delivery device according to claim 19, further comprisinga needle that is configured to protrude from the distal end of the firstportion.
 26. The medicament delivery device according to claim 19,wherein the first and second portions of the housing comprise respectiveperipheral walls, and the peripheral wall of one of the first and secondportions is configured to be received within the peripheral wall of theother one of the first and second portions.
 27. The medicament deliverydevice according to claim 19, wherein the housing is configured suchthat the second portion is slidable relative to the first portion fromthe initial position to the primed position.
 28. The medicament deliverydevice according to claim 19, wherein at least one of the first orsecond portions comprises a screw thread.
 29. A medicament deliverydevice according to claim 19, further comprising a latch configured toresist movement of the second portion relative to the first portion fromthe primed position to the initial position.
 30. The medicament deliverydevice according to claim 19, wherein the first portion of the housingcomprises a filling port for supplying the reservoir with medicament.31. The medicament delivery device according to claim 19, wherein thesecond portion of the housing comprises a filling port for supplying thereservoir with medicament.
 32. The medicament delivery device accordingto claim 19, wherein the first and second portions of the housing eachcomprise a filling port for supplying the reservoir with medicament. 33.The medicament delivery device according to claim 19, wherein themedicament delivery device is a large volume device.
 34. The medicamentdelivery device according to claim 19, wherein the reservoir contains amedicament.
 35. The medicament delivery device according to claim 19,wherein the reservoir is located between the first and second portionsof the housing.
 36. The medicament delivery device according to claim19, wherein the actuator is at least partially received in the secondportion of the housing.
 37. The medicament delivery device according toclaim 19, wherein the first and second portions of the housing define achamber that receives the dispensing mechanism.
 38. A method ofpreparing a medicament delivery device comprising a housing comprising afirst portion and a second portion, a dispensing mechanism comprising areservoir disposed in the housing, and an actuator, the methodcomprising: positioning a distal end of the first portion in proximityto an injection site of a patient; and moving the second portion towardsthe distal end of the first portion from an initial position to a primedposition, wherein actuation of the actuator is impeded such thatoperation of the dispensing mechanism is prevented when the secondportion is in the initial position, and the actuator is moveablerelative to the housing to operate the dispensing mechanism to dispensemedicament from the reservoir to the injection site when the secondportion is in the primed position.